Mixtures of sabadilla alkaloids and azadirachtin and uses thereof

ABSTRACT

The present invention is directed to pesticidal mixtures comprising sabadilla alkaloids and azadirachtin and methods of controlling pests including insects and mites by application of pesticidal mixtures comprising sabadilla alkaloids and azadirachtin.

FIELD OF THE INVENTION

The present invention is directed to pesticidal mixtures comprisingsabadilla alkaloids and azadirachtin and methods of controlling pestsincluding insects and mites by application of pesticidal mixturescomprising sabadilla alkaloids and azadirachtin.

BACKGROUND OF THE INVENTION

Arthropod pests are one of the major threats to human welfare and exertcontinued stress on the food supply and transmit a broad array ofmedical and veterinary diseases. Synthetic insecticides played asignificant role and in many ways ushered in modern agriculture and pestcontrol. However, the widespread use of synthetic insecticides alsocreated numerous environmental challenges. The acute effects ofsynthetic pesticides on professional applicators and other end users arewell-known but the chronic long term human health effects can be equallyserious. Further, the use of synthetic insecticides has led to thedevelopment of resistant insect populations. Insecticide resistance is acomplex phenomenon underlined by a diverse array of physiologicalmechanisms. Major mechanisms that are responsible for the development ofinsecticide resistance are metabolic detoxification, target sitemutation, reduced cuticular penetration and behavioral avoidance.

Integrated Pest Management (“IPM”) is a holistic approach to pestmanagement. A fundamental aspect of insecticide utilization under thebroader framework of IPM is the management of insecticide resistance(IRM) by the utilization of insecticide combinations that reduce therate of resistance development. A combination of insecticides withdifferent modes of action is fundamentally a concept based upon the ideaof redundant killing of target insects. Insects adapted to one of theactive ingredient in the combination product will still be killed by theother active ingredient. Mixtures can also reduce the amount ofpesticides applied in the environment and the environmental impactassociated with pesticide applications.

Most botanical insecticides are readily biodegradable and significantlyless harmful to the environment and users than synthetic insecticides.The very short environmental persistence, usually less than 24 hours, ofplant derived insecticides is favorable to the survival of non-target,beneficial parasites and predators which are important components ofIPM. Unlike conventional insecticides which are typically based on asingle active ingredient, plant derived insecticides usually comprise anarray of chemical compounds that affect both behavioral andphysiological functions of the target arthropods. The probability ofpest resistance developing to plant derived insecticides is less thanthat for synthetic pesticides because these mixtures may have a varietyof modes of action.

One effective naturally derived pesticide is found in the tissues ofmany of the plants of the genus Schoenocaulon, commonly referred to assabadilla. The species with the longest history of use, and the mostreadily available, is Schoenocaulon officinale. The plant is indigenousto Central and South America and its seeds have been used for centuriesfor their insecticidal properties. The seeds contain several alkaloidsincluding veratridine and cevadine, both of which are known to be activeagainst arthropods.

Azadirachtin is another naturally derived pesticide found in neem tree(Azadirachta indica) oil. Azadirachtin is effective against over 200species of insects by dissuading feeding and disrupting growth. Further,azadirachtin demonstrates very low toxicity to mammals and isbiodegradable.

Thus, there is a need in the art for pesticide combinations that containnaturally derived pesticides that decrease health concerns to humans andalso decrease the risk of the development of pesticide resistance.

SUMMARY OF THE INVENTION

In one aspect, the present invention is directed to pesticidal mixturesof sabadilla alkaloids and azadirachtin.

In another aspect, the present invention is directed to methods ofcontrolling pests, including insects and mites, comprising applying aneffective amount of a mixture of sabadilla alkaloids and azadirachtin.

In a preferred aspect, the sabadilla alkaloids are derived fromSchoenocaulon officinale.

DETAILED DESCRIPTION OF THE INVENTION

Applicant unexpectedly discovered that pesticidal mixtures of sabadillaalkaloids and azadirachtin provided enhanced pesticidal activitycompared to either pesticide alone. Further, Applicant discovered thatpesticidal mixtures of sabadilla alkaloids and azadirachtin were capableof controlling a large variety of arthropods.

The present invention is directed to pesticidal mixtures comprising aneffective amount of sabadilla alkaloids and azadirachtin.

Sabadilla alkaloids may be derived from any species of Schoenocaulon.The genus Schoenocaulon includes the following species: S. calcicola, S.caricifolium, S. comatum, S. conzattii, S. dubium (alt. S. gracile), S.framei, S. ghiesbreghtii (alt. S. drummondii, S. yucatanense), S.ignigenum, S. intermedium, S. jaliscense, S. macrocarpum (alt. S.lauricola), S. madidorum, S. megarrhizum, S. mortonii, S. oaxacense, S.obtusum, S. officinale, S. pellucidum, S. plumosum, S. pringlei, S.rzedowskii, S. tenorioi, S. tenue, S. tenuifolium, S. texanum, and S.tigrense. In a preferred embodiment the sabadilla alkaloids are derivedfrom S. officinale. In another preferred embodiment the sabadillaalkaloids are veratridine and cevadine.

As used herein, all numerical values relating to amounts, weightpercentages and the like are defined as “about” or “approximately” eachparticular value, namely, plus or minus 10%. For example, the phrase “atleast 5% by weight” is to be understood as “at least 4.5% to 5.5% byweight.” Therefore, amounts within 10% of the claimed values areencompassed by the scope of the claims.

The term “effective amount” means the amount of the formulation thatwill control the target pest. The “effective amount” will vary dependingon the mixture concentration, the type of pest(s) being treated, theseverity of the pest infestation, the result desired, and the life stageof the pest during treatment, among other factors. Thus, it is notalways possible to specify an exact “effective amount.” However, anappropriate “effective amount” in any individual case may be determinedby one of ordinary skill in the art.

In a preferred embodiment, the ratio of sabadilla alkaloids toazadirachtin is from about 1:110 to about 42:1, preferably from about1:2 to about 42:1 and from about 1:110 to about 1:1 and from about 1:10to about 10:1 and from about 1:5 to about 5:1 and from about 1:2 toabout 2:1.

In another preferred embodiment, the pesticidal mixtures of the presentinvention may contain one or more excipients selected from the groupconsisting of solvents, anti-caking agents, stabilizers, defoamers, slipagents, humectants, dispersants, wetting agents, thickening agents,emulsifiers, penetrants, adjuvants, synergists, polymers, propellantsand/or preservatives.

The present invention is further directed to methods of controlling apest comprising applying a pesticidal mixture comprising an effectiveamount of sabadilla alkaloids and azadirachtin to the pest or the pest'senvironment.

In a preferred embodiment, the pest is selected from an insect and amite.

In an embodiment, the pest controlled is selected from the groupconsisting of aphids (Homoptera), whiteflies (Hemiptera), thrips(Thysanoptera), bed bugs (Hemiptera), fleas (Siphonaptera),caterpillars/worms (Lepidoptera), beetles (Coleoptera), cockroaches(Blattodea), flies (Diptera), ants (Hymenoptera), mosquitoes (Culicidae)and mites (Acari). In a preferred embodiment, the pest controlled areselected from the group consisting of common bed bugs (Cimexlectularius), green peach aphids (Myzus persicae), house fly (Muscadomestica), yellow fever mosquito (Aedes aegypti), southern housemosquito (Culex quinquefasciatus), African malaria mosquito (Anophelesgambiae), common malaria mosquito (Anopheles quadrimaculatus) and Germancockroach (Blattella germanica).

The pesticidal mixtures of the present invention can be applied by anyconvenient means. Those skilled in the art are familiar with the modesof application including spraying, brushing, soaking, in-furrowtreatments, or side-dressing.

In a preferred embodiment, sabadilla alkaloids are applied to the pestor the pest's environment at a rate from about 1 to about 1,000 gramsper hectare (“g/HA”), preferably from about 10 to about 700 g/HA andmost preferably from about 22 to about 560 g/HA.

In a preferred embodiment, azadirachtin is applied to the pest or thepest's environment at a rate from about 1 to about 100 g/HA, morepreferably from about 10 to about 70 g/HA and most preferably from about13 to about 54 g/HA.

In another preferred embodiment, the pesticidal mixtures of the presentinvention comprise form about 0.05% to about 0.5% w/w sabadillaalkaloids.

In another preferred embodiment, the pesticidal mixtures of the presentinvention comprise form about 0.5% to about 5.5% w/w azadirachtin.

As used herein, “control” a pest or “controlling” pest(s) refers tokilling, incapacitating, repelling, or otherwise decreasing the negativeimpact of the pest on plants or animals to a level that is desirable tothe grower or animal.

As used herein, “pest's environment” refers to any area that the pest ispresent during any life stage. One environment likely to be treated bythe methods of the present invention includes the plants that the pestis living on and the surrounding soil. The pest's environment may alsoinclude harvested plants, gardens, fields, greenhouses, or otherbuildings, and various indoor surfaces and structures, such as furnitureincluding beds, and furnishings including books, clothing, etc.

The articles “a,” “an” and “the” are intended to include the plural aswell as the singular, unless the context clearly indicates otherwise.For example, the methods of the present invention are directed tocontrolling “pest” but this can include control of a multiple pests(such as a more than one insect or more than one insect species or morethan one mite or more than one mite species).

The following examples are intended to illustrate the present inventionand to teach one of ordinary skill in the art how to use the extracts ofthe invention. They are not intended to be limiting in any way.

EXAMPLES

Neemix® 4.5 was used as the source of azadirachtin. Neemix® is aregistered trademark of Certis USA, LLC.

Example 1 German Cockroach

In this study, the response of the German cockroach (Blattellagermanica) to application of a 1:10, 1:1, 1:110 and 1:11 ratio ofsabadilla (S. officinale) alkaloids to azadirachtin will be observed.Specifically, sabadilla alkaloids and azadirachtin will be applied tothe pest at the respective rates of: 1) 0.05% w/w to 0.5% w/w, 2) 0.5%w/w to 0.5% w/w, 3) 0.05% w/w to 5.5% w/w and 4) 0.5% w/w to 5.5% w/w.

The results of the study are predicted to show enhanced pesticidalactivity.

Example 2 House Fly

In this study, the response of the house fly (Musca domestica) toapplication of a 1:10, 1:1, 1:110 and 1:11 ratio of sabadilla (S.officinale) alkaloids to azadirachtin will be observed. Specifically,sabadilla alkaloids and azadirachtin will be applied to the pest at therespective rates of: 1) 0.05% w/w to 0.5% w/w, 2) 0.5% w/w to 0.5% w/w,3) 0.05% w/w to 5.5% w/w and 4) 0.5% w/w to 5.5% w/w.

The results of the study are predicted to show more than an additiveeffect when application occurs at the larval stage. One can determinethat the response is synergistic using the following formula: %Cexp=A+B−(AB/100).

% Cexp=A+B−(AB/100), where % Cexp is the expected efficacy and “in whichA and B are the control levels given by the single [insecticides]. Ifthe ratio between the experimentally observed efficacy of the mixtureCobs and the expected efficacy of the mixture is greater than 1,synergistic interactions are present in the mixture.” (Gisi,Synergisitic Interaction of Fungicides in Mixtures, The AmericanPhytopathological Society, 86:11, 1273-1279,1996). Adopting aconservative approach, Applicant determined synergy to be present atratios of ≥1.1.

Example 3 Common Bed Bug

In this study, the response of the common bed bug (Cimex lectularius) toapplication of a 1:10, 1:1, 1:110 and 1:11 ratio of sabadilla (S.officinale) alkaloids to azadirachtin will be observed. Specifically,sabadilla alkaloids and azadirachtin will be applied to the pest at therespective rates of: 1) 0.05% w/w to 0.5% w/w, 2) 0.5% w/w to 0.5% w/w,3) 0.05% w/w to 5.5% w/w and 4) 0.5% w/w to 5.5% w/w.

The results of the study are predicted to show enhanced pesticidalactivity.

Example 4 Green Peach Aphid

In this study, the response of the green peach aphid (Myzus persicae) toapplication of a 1.7:1, 41.7:1, 1:2.4 and 10.4:1 ratio of sabadilla (S.officinale) alkaloids to azadirachtin will be observed. Specifically,sabadilla alkaloids and azadirachtin will be applied to the pest at therespective rates of: 1) 22 g/HA and 54 g/HA; 2) 22 g/HA and 13 g/HA; 3)560 g/HA and 54 g/HA; and 4) 560 g/HA and 13g/HA.

The results of the study are predicted to show more than an additiveeffect. One can determine that the response is synergistic using thefollowing formula: % Cexp=A+B−(AB/100).

What is claimed is:
 1. A pesticidal mixture comprising an effectiveamount of sabadilla alkaloids and azadirachtin.
 2. The mixture of claim1, wherein the sabadilla alkaloids are derived from Schoenocaulonofficinale.
 3. The mixture of claim 1, wherein the sabadilla alkaloidsare veratridine and cevadine.
 4. The mixture of claim 1, wherein theratio of sabadilla alkaloids to azadirachtin is from about 1:110 toabout 42:1.
 5. The mixture of claim 1, wherein the ratio of sabadillaalkaloids to azadirachtin is from about 1:2 to about 42:1.
 6. Themixture of claim 1, wherein the ratio of sabadilla alkaloids toazadirachtin is from about 1:110 to about 1:1.
 7. The mixture of claim1, wherein the sabadilla alkaloids are at a concentration from about0.05% to about 0.5% w/w, wherein w/w denotes weight by total weight ofthe mixture.
 8. The mixture of claim 1, wherein the azadirachtin are ata concentration from about 0.5% to about 5.5% w/w, wherein w/w denotesweight by total weight of the mixture.
 9. The mixture of claim 1 furthercomprising one or more excipients selected from the group consisting ofsolvents, anti-caking agents, stabilizers, defoamers, slip agents,humectants, dispersants, wetting agents, thickening agents, emulsifiers,penetrants, adjuvants, synergists, polymers, propellants and/orpreservatives.
 10. A method of controlling a pest comprising applying apesticidal mixture comprising an effective amount of sabadilla alkaloidsand azadirachtin to the pest or the pest's environment.
 11. The methodof claim 10, wherein the pest is at least one of an insect and a mite.12. The method of claim 10, wherein the pest is selected from the groupconsisting of aphids (Homoptera), whiteflies (Hemiptera), thrips(Thysanoptera), bed bugs (Hemiptera), fleas (Siphonaptera),caterpillars/worms (Lepidoptera), beetles (Coleoptera), cockroaches(Blattodea), flies (Diptera), ants (Hymenoptera), and mites (Acari). 13.The method of claim 10, wherein the pest is selected from the groupconsisting of common bed bugs (Cimex lectularius), green peach aphids(Myzus persicae), house fly (Musca domestica), yellow fever mosquito(Aedes aegypti), southern house mosquito (Culex quinquefasciatus),African malaria mosquito (Anopheles gambiae), common malaria mosquito(Anopheles quadrimaculatus) and German cockroach (Blattella germanica).14. The method of claim 10, wherein the sabadilla alkaloids are appliedto the pest or the pest's environment at a rate from about 1 to about1,000 grams per hectare.
 15. The method of claim 10, wherein thesabadilla alkaloids are applied to the pest or the pest's environment ata rate from about 10 to about 700 grams per hectare.
 16. The method ofclaim 10, wherein the sabadilla alkaloids are applied to the pest or thepest's environment at a rate from about 22 to about 560 grams perhectare.
 17. The method of claim 10, wherein the azadirachtin is appliedto the pest or the pest's environment at a rate from about 1 to about100 grams per hectare.
 18. The method of claim 10, wherein theazadirachtin is applied to the pest or the pest's environment at a ratefrom about 10 to about 70 grams per hectare.
 19. The method of claim 10,wherein the azadirachtin is applied to the pest or the pest'senvironment at a rate from about 13 to about 54 grams per hectare.